Rational Biosynthetic Engineering for Optimization of Geldanamycin Analogues

Tailor made : We report the rational biosynthesis of C15 hydroxylated non‐quinone geldanamycin analogues by site‐directed mutagenesis of the geldanamycin polyketide synthase (PKS), together with a combination of post‐PKS tailoring genes. Rational biosynthetic engineering allowed the generation of geldanamycin derivatives, such as DHQ3 illustrated in the figure, which had superior pharmacological properties in comparison to the parent compound.

     

Shrinkage behavior and interfacial diffusion in Ni-based internal electrodes with BaTiO3 additive

The effects of particle size of starting materials and amount of a BaTiO₃ additive on the shrinkage behavior and elemental diffusion in Ni-based internal electrodes have been investigated in order to control the shrinkage of the internal electrode in multilayer ceramic capacitors (MLCCs). Two kinds of Ni and BaTiO₃ powders were used with different particle sizes. Volume shrinkage over the range of 700–1300 °C at 150 °C intervals and linear shrinkage during sintering were measured for starting materials and composites in a reducing atmosphere. The interfaces of Ni/BaTiO₃ composites with 90:10 and 70:30 volume ratios, respectively, were investigated using TEM. Composites with bimodal Ni powder show less shrinkage than those with monomodal Ni powder, showing less shrinkage in monolith Ni of bimodal particle size. The shrinkage behavior is changed during sintering with increasing amounts of BaTiO₃ additives in both Ni-based composites. The particle size of the BaTiO₃ additive affects the shrinkage behavior of composites, without the additional amount affecting the final shrinkage. A reaction layer of about 300 nm wide is observed at the interface between the Ni and BaTiO₃ powders in composites, in which elemental Ni diffuses into the BaTiO₃ without counterdiffusion.     

Structural estimation of particle arrays at air–water interface based on silica particles with well‐defined and highly grafted poly(methyl methacrylate)

Silica nanoparticles with well‐defined, highly grafted dense poly(methyl methacrylate) (MMA) were prepared by surface‐initiated activators regenerated by electron transfer for atom transfer radical polymerization (ARGET ATRP) of methyl methacrylate with an initiator‐fixed silica particle in the presence of air. Two different polymerizations of MMA were carried out under the same conditions using tris[2‐(dimethylamino)ethyl]amine (Me₆TREN) and N,N,N′,N′,N″‐pentamethyldiethylene‐triamine (PMDETA) as the ligand, respectively. In the CuCl₂/PMDETA system, polymerization appeared to be more controlled with a lower polydisperisty compared with the CuCl₂/Me₆TREN system. The monolayer of these particles was formed at the air–water interface using Langmuir‐Blodgett (LB) technique. Multilayers of the particles were fabricated by repetition of LB depositing. A surface pressure–area (π–A) measurement and SEM observation were used to characterize the particle arrays. POLYM. ENG. SCI., 2010. © 2009 Society of Plastics Engineers     

Nonlinear finite element method models for ultimate strength analysis of steel stiffened-plate structures under combined biaxial compression and lateral pressure actions—Part II: Stiffened panels

The present paper (Part II) is a sequel to the previous paper (Part I) [Paik JK, Seo JK. Nonlinear finite element method models for ultimate strength analysis of steel stiffened-plate structures under combined biaxial compression and lateral pressure actions—Part I: Plate elements. Thin-Walled Struct 2008, this issue, doi:10.1016/j.tws.2008.08.005.] on the application of nonlinear finite element methods for ultimate strength analysis of steel stiffened-plate structures under combined biaxial compression and lateral pressure actions. In contrast to Part I dealing with plate elements, the present paper (Part II) treats stiffened panels surrounded by strong support members such as longitudinal girders and transverse frames. In similar to Part I, some important factors of influence such as structural dimensions, initial imperfections, loading types and computational techniques in association with ultimate limit states are studied. Some useful insights in terms of nonlinear finite element method modeling are developed using ANSYS code together with the ALPS/ULSAP semi-analytical method, the latter being for the purpose of a comparison.     

Interfacial reaction between 42Sn-58Bi solder and electroless Ni-P/immersion Au under bump metallurgy during aging

The interfacial reaction between 42Sn-58Bi solder (in wt.% unless specified otherwise) and electroless Ni-P/immersion Au was investigated before and after thermal aging, with a focus on the formation and growth of an intermetallic compound layer, consumption of under bump metallurgy (UBM), and bump shear strength. The immersion Au layer with thicknesses of 0 μm (bare Ni), 0.1 μm, and 1 μm was plated on a 5-μm-thick layer of electroless Ni-P (with 14–15 at.% P). The 42Sn-58Bi solder balls were then fabricated on three different UBM structures by using screen printing and pre-reflow. A Ni₃Sn₄ layer formed at the joint interface after the pre-reflow for all three UBM structures. On aging at 125°C, a quaternary phase, identified as Sn₇₇Ni₁₅Bi₆Au₂, was observed above the Ni₃Sn₄ layer in the UBM structures that contain Au. The thick Sn₇₇Ni₁₅Bi₆Au₂ layer degraded the integrity of the solder joint, and the shear strength of the solder bump was about 40% less than the nonaged joints.     

Isolation of the third capsule-associated gene, CAP60, required for virulence in Cryptococcus neoformans

A polysaccharide capsule is one of the most important virulence factors for the pathogenic fungus Cryptococcus neoformans. We previously characterized two capsule-associated genes, CAP59 and CAP64. To further dissect the molecular mechanism of capsule synthesis, 16 acapsular mutants induced by 4-nitroquinoline-1-oxide were obtained. The acapsular phenotype of one of these mutants was complemented. The cloned gene was designated CAP60, and deletion of this newly described capsule-associated gene resulted in an acapsular phenotype. The proposed 67-kDa Cap60p contains 592 amino acids and appears to have a putative transmembrane domain close to the N terminus. DNA sequence analysis revealed that CAP60 has similarity to CAP59 at the center portion of its coding regions. Contour-clamped homogeneous electric field blot analysis suggested that these two genes are on the same chromosome. CAP60 and CAP59, however, could not be functionally substituted for each other by direct complementation or by domain swap experiments. In addition, CAP60 is closely linked to a gene which is similar to a cellulose growth-specific gene of Agaricus bisporus, CEL1. Immunogold electron microscopy studies of the epitope-tagged CAP60 gene revealed that Cap60p was primarily localized to the nuclear membrane. Animal model studies indicated that CAP60 is essential for virulence. Thus, CAP60 is required for both capsule formation and virulence.     

POEMS syndrome in a patient with diabetic ketoacidosis: case report and review

This article summarise the main data in the literature on the role of bacteriological contamination of the dialysate fluid in inflammatory reactions in hemodialysis. Pyrogenic substances of small molecular weight from Gram-negative bacteria grown in dialysate can pass across intact dialyzer membrane to stimulate cytokine production by peripheral blood mononuclear cells. Cellulosic hemodialysis membranes are more permeable to endotoxins than synthetic membranes. Polysulfone membranes and polyamide membranes are able to adsorb bacterial toxins on the dialysate side. The diffusive transfer of bacterial products across dialysis membrane from dialysate fluid was demonstrated. Transmembrane passage of cytokine-inducing bacterial products across reprocessed dialyzers is greater than across new dialyzers. Bacteriological contamination of the dialysate fluid is a problem which must be considered with much more care by nephrologists, especially as LAL test is unable to detect all the bacterial products which can contaminate the dialysate fluid.     

Absence of normal activation of the left anterior fusiform gyrus during naming in left temporal lobe epilepsy

Patients with left temporal lobe epilepsy (TLE) often have impaired naming. We studied 13 patients with left TLE and 10 healthy control subjects with [(15)O]H2O PET during visual confrontation naming. Statistical mapping detected multiple regions of significant cerebral blood flow increases within individuals. The left fusiform gyrus was activated in nine healthy subjects, but only in two patients with TLE (a significant difference, p < 0.001). Other activation sites were more variable in healthy subjects and those with TLE. Impaired naming ability may be associated with a lack of increased cerebral blood flow in the left fusiform gyrus in TLE.